Nature of "Tau" immunoreactivity in normal myonuclei and inclusion body myositis

Sarcoplasmic accumulation of phosphorylated-tau has been widely stated to occur in and contribute to the pathogenesis of muscle disease in inclusion body myositis. Twenty inflammatory myopathy and 10 normal muscle samples along with a range of other tissues were stained with anti-"tau" antibodies (tau-5, pS422, and SMI-31). Myonuclear and sarcoplasmic fractions were prepared using differential solubilization and laser-capture microdissection, and immunoblots were performed using pS422 and SMI-31 antibodies. All three antibodies demonstrated anti-tau immunoreactivity in myonuclei from normal and diseased muscle, but not in nuclei from other tissues. Western blots showed pS422 and SMI-31 immunoreactivity against nuclear proteins outside the region expected for phosphorylated-tau. Antibodies previously reported to indicate abnormal accumulation of phosphorylated-tau in IBM myofibers react to normal myonuclei and recognize proteins other than tau. Normal myonuclei contain neurofilament H or other unidentified 200 kDa proteins with similar phosphorylated motifs accounting for SMI-31 immunoreactivity.